Anti-Microbial Implant

ABSTRACT

Non-load-bearing, drug-eluting components that can be added to load bearing spinal implants.

BACKGROUND OF THE INVENTION

Implant-associated infections are deep wound infections that occur at ornear the site of an implanted device and frequently require a secondsurgery to remove the implant. (refs. 1,2) Retrospective studies ofspinal surgery procedures involving implants report infection rates of1.7% to 17%. (refs. 3-6) The highest incidences of implant-associatedinfections have been reported for spinal trauma procedures (9-17%) (ref.7) and scoliosis/deformity procedures (1.7-11%) (refs. 8-11). Theaverage cost of an orthopedic implant-associated infection is $15,000(ref. 12), and the cost for scoliosis instrumentation is reported to be$65,000. (ref. 13) The cost of treating individual infections has beenestimated as roughly $22,170 per occurrence. The cost of implantinfections in spine surgery divided by the total number of spinepatients is estimated to be about $2,400/patient. Third-party payers andpatients assume some of these costs, but hospitals and physicians areasked to absorb the remainder.

This cost data suggests the need for a product that minimizes infectionrates or mitigates the consequences of infections in spine surgery andthat costs less than $2,400 per surgery. Such a product would bevaluable to patients, surgeons, hospitals, and medical insurers whilealso having equitable benefits for healthcare economics.

There are no commercially available spinal products specificallydesigned to treat or manage implant-associated infections in spinesurgery. Although technology exists in the areas of anti-infectivecoatings and drug-eluting materials, no technology has been developedthat describes spinal device components with anti-infective properties.

Some conventional technologies for preventing or managing infectionassociated with implants are provided in the following patent documents:EP754064, entitled “Polymer Coating for Orthopedic Devices”; EP792654,entitled “Antimicrobial Pin Sleeve”; US2002/0029043, entitled “SilverBone Screw” and assigned to Synthes; US2003/0036761, entitled“Pharmacological Pin Sleeve” and assigned to Smith & Nephew Richards;US2005/0031665, entitled “Orthopedic Screw Delivery System”;US2005/0059972, entitled “Screw Assembly with Antimicrobial Properties”;US2006/0093646, entitled “Drug Eluting Orthopedic Hip Implant”; U.S.Pat. No. 4,442,133, entitled “Preoperative Anti-Biotic Graft Coating”;U.S. Pat. No. 4,476,590, entitled “Silver Antimicrobial surgicalimplants”; U.S. Pat. No. 5,098,434, entitled “Porous Coated Bone Screw”;U.S. Pat. No. 6,514,517, entitled “Prevention of Biofilms” and assignedto Ethicon; U.S. Pat. No. 6,575,945, entitled “Prevention of Biofilms”;U.S. Pat. No. 6,663,634, entitled “Bone Screw” and assigned to Synthes;U.S. Pat. No. 6,921,390, entitled “Antibiotic Sleeve” and assigned toBostonScientific; U.S. Pat. No. 6,936,270, entitled “Orthopedic ScrewDrug Delivery System and assigned to Control Delivery Systems, Inc; U.S.Pat. No. 7,066,938, entitled “Snap-On Rod Connector” and assigned toDePuy Spine;, and WO2002036175, entitled “Orthopedic Screw Drug DeliverySystem” and assigned to Control Delivery Systems.

WO1998003209, entitled “Screw Cap contoured” describes a non-loadbearing screw cap that facilitates revision of the implanted screw.

SUMMARY OF THE INVENTION

The present invention relates to non-load-bearing, drug-elutingcomponents that can be attached to load-bearing spinal implants.Preferably, these components elute anti-microbial compounds into theregions in and around the load bearing spinal implants.

The drug-eluting device of the present invention is designed to be anon-load-bearing component (such as a screw cap or rod cover) that fitsonto or over conventional structural spinal implants. The geometry ofthe drug-eluting device of the present invention may be designed touniquely conform to the spinal products of a single manufacturer, or thedevice could be made to work with a wide variety of product geometries.

Some embodiments of the present invention take the form of animplantable “screw-spacer” between screw heads or of a “rod-spacer”similar in form to a transverse cross connector. In these embodiments,the device acts as a non-load bearing cover or strut of materialassociated with the implant construct. Thus, the invention can beload-bearing or non-load bearing.

Drug-eluting devices provide benefits over systemic drug-deliverybecause the amount of the dose, the location of the dose and theduration of the dose can be controlled by device design. Fordrug-eluting devices, local drug dose and duration are controlled by thecarrier material's resorption rate and geometric surface area, and/orthe drug's diffusion in tissue. Providing an anti-infectivefunctionality as a component of a spine instrumentation system may alsoallow for simpler product regulation as a combination device. It mayalso allow the drug-eluting functionality to be manufactured, packaged,stored, and distributed separately from the associated structural rodsand screws. Lastly, the device could be used for the prophylactictreatment of post-surgical infections.

In one method of using the present invention, the drug-eluting device ofthe present invention is attached in the operative setting to animplanted orthopedic or spinal product for the purpose of preventing theinoculation or growth of microbes on or near the implant.

In another method of using the present invention, the drug-elutingdevice of the present invention treats an infected implant byconcentrating anti-microbial pharmaceutical compounds in the region ofthe biofilm on the implant surface. Thus, antibiotics leach from theinvention and concentrate on, around, or near the biofilm-coatedimplant, wherein little or no antibiotic leaches away from the implant.The directionality of this device enables the use of very highconcentrations of antibiotics or very aggressive antibiotic molecules(e.g., vancomycin instead of gentamicin).

Also, drug-eluting devices of the present invention can be furtherdesigned to elute drugs over a prolonged period of time to increasetheir local efficacy.

The drug-eluting implant of the present invention may be either asurface-eroding device or a bulk eroding biodegradable device containingan adequate anti-bacterial pharmaceutical, such as gentamicin ortobramycin. As the drug-eluting implant erodes or degrades, theanti-bacterial pharmaceutical contained in the device leaches ordiffuses into surrounding tissues for a local anti-microbial action.Because the drug is not delivered systemically, many drug-related sideeffects can be minimized and the “minimum effective concentration” (MEC)of the drug can be maintained at the site of need for a prolonged periodof time.

Maintaining a high local concentration of an anti-bacterial drug shouldgreatly diminish acute wound infections (99% of all hospital infections)and also decrease implant-associated infections (1-2% of all infections,but devastating when present).

Embodying the invention in a separate device that physically attaches tothe structural spinal implant avoids many of the problems associatedwith drug-coated devices (inventory, sterilization, packaging, handling,shelf-life, altered biomechanics, etc.) and streamlines the regulatoryprocess.

Therefore, in accordance with the present invention, there is provided aspinal screw assembly, comprising:

-   -   a) a load bearing spinal component,    -   b) a non-load bearing spinal component comprising a        pharmaceutical compound,        wherein the non-load bearing spinal component is attached to the        load bearing spinal component.

Therefore, in accordance with the present invention, there is provided amethod of making a spinal screw assembly, comprising the steps of:

-   -   a) providing a load bearing spinal component,    -   b) providing a non-load bearing spinal component comprising a        pharmaceutical compound,    -   b) attaching the non-load bearing spinal component to the load        bearing spinal component.

DESCRIPTION OF THE FIGURES

FIG. 1 a discloses a cross section of a bone screw cap of the presentinvention having a flange.

FIG. 1 b discloses a cross section of the bone screw cap of FIG. 1 afitted upon a bone screw head.

FIG. 2 discloses a cross section of a bone screw cap of the presentinvention having a central shank.

FIG. 3 discloses a cross section of the bone screw cap of FIG. 2 fittedupon a bone screw head.

FIG. 4 discloses a drug concentration around a spinal assembly having abone screw cap of the present invention.

FIG. 5 discloses a cross section of a bone screw cap of the presentinvention having a recess.

FIG. 6 discloses a cross section of the bone screw cap of FIG. 5 fittedupon a bone screw head.

FIG. 7 discloses a cross section of a plurality of bone screw capshoused in a spring loaded container.

FIG. 8 discloses a plurality of bone screw caps of the present inventionjoined together.

FIG. 9 discloses an exploded version of a plurality of bone screw capposts joined together with a cover.

FIG. 10 discloses an integral version of a plurality of bone screw capsjoined together.

FIG. 11 discloses a cross section of bone screw cap having a cover of afirst material and a post of a second material.

FIG. 12 discloses a split cover, a split ring and a coil for covering arod.

FIG. 13 discloses a drug concentration around a spinal assembly having arod cover of the present invention.

FIG. 14 a discloses a cross section of a spinal assembly comprising apolyaxial bone screw, a rod and a rod cover.

FIG. 14 b disclose a spinal rod cover.

FIG. 14 c discloses cross sections of a spinal rod cover and rod.

FIG. 15 a discloses a spinal rod cover having slits.

FIG. 15 b discloses a spinal rod cover having slits and depressions.

FIGS. 16 a and 16 b disclose a machine for making spinal rod covers.

FIG. 17 discloses a spinal rod cover having slits and depressions.

FIGS. 18-20 shows graphs of the concentration profiles of various drugdelivery approaches over time.

FIGS. 21 a-21 e represent embodiments of the rod cover havingextensions.

FIGS. 22 a-22 e represent embodiments of the screw cap havingextensions.

DETAILED DESCRIPTION OF THE INVENTION

Now referring to FIGS. 1 a and 1 b, there is provided a bone screw cap 1loaded with a pharmaceutical compound, and comprising:

-   -   a) a cover 3 having a perimeter 5 and a center 7,    -   b) a shank 9 extending downwardly from the perimeter of the        cover,    -   c) a flange 11 extending inwardly from the shank and adapted to        engage a recess in a side of the bone screw,        wherein the shank fits substantially closely to an outer contour        12 of a head 13 of a bone screw 15.

Now referring to FIGS. 2 and 3, there is provided a bone screw cap 21loaded with a pharmaceutical compound, and comprising:

-   -   a) a cover 23 having a perimeter 25 and a center 27,    -   b) a shank 29 extending downwardly from the center of the cover,        wherein the shank fits substantially closely to an inner contour        31 of a head 33 of a bone screw 35.

The bone screw cap of the present invention is preferably adapted to fitover the conventional polyaxial pedicle screw that is used in spinalsurgery. In many embodiments, the pedicle screw has a substantiallycylindrical upper portion (or head) and the cap is adapted to fit overthis cylindrical portion. In some embodiments, the cap is a snap-on typehaving features that mate with corresponding mating features provided onthe cylindrical upper portion of the pedicle screw. Pharmaceuticalseluted from the bone screw cap can provide their highest concentrationin and around the bone screw, which is the site of the most complicatedgeometry of the conventional spinal implant, and at which it ishypothesized that latent microbes gain a foothold and proliferate. Thedose of pharmaceutical delivered by the screw cap as well as itsduration can be increased by increasing the thickness of the cap.

Now referring to FIG. 4, there is provided a side view of a screw cap 37of the present invention attached to a spinal implant system that isimplanted in a spine, wherein the spinal implant system comprises rods41 and screws 43. There is a high concentration [C] of thepharmaceutical present in the regions directly adjacent the screw cap,and this concentration lessens with increasing distance from the screwcap. This embodiment also provides a relatively severe localconcentration gradient around the screw cap. The severity of thegradient is likely due to the relatively small size of the screw caprelative to the overall implant system. The elution profile of thepharmaceutical will likely change as the screw cap degrades ordissolves, thereby making the concentration a function of location, capgeometry, implant system geometry, and time.

In some embodiments, the means for connecting the cap to the bone screwcomprises an adhesive or a curing composition.

In some embodiments, and now referring to FIGS. 5-6, there is provided apress-fit bone screw cap 45 having:

-   -   a) a cover 47 having a perimeter 49 and a center 51,    -   b) a shank 53 extending downwardly from the perimeter of the        cover, and    -   c) a recess 55 extending into the shank and adapted to engage a        flange 57 extending outwardly from a head 59 of a bone screw 61.        This cap attaches to external screw head features, such as a        flange extending radially from the cylindrical portion of the        conventional polyaxial pedicle screw.

Now referring to FIG. 7, in some embodiments, the press-fit screw caps63 of the present invention can be stored in a stack-wise fashion in aspring-loaded 65 dispenser 67 and used on an as-needed basis.

Now referring to FIG. 8, in some embodiments, a plurality of connectedpress-fit screw caps 69 of the present invention can be provided in atip-to-toe fashion. Individual caps are separated from the assembly bybreaking them at a fracture point 71 present between the tip of one capand the toe of the adjacent cap, and used on an as-needed basis. Thedesign of this embodiment lends itself to manufacture by an extrusionprocess.

Still referring to FIG. 8, there is provided an a plurality of connectedbone screw caps 69 loaded with a pharmaceutical compound, wherein eachcap comprises a:

-   -   a) a cover 73 having a perimeter 75 and a center 77,    -   b) a shank 79 having a first end 81 connected to the center of        the cover and a second end 83,        wherein the shank fits substantially closely to an inner contour        of a head of a bone screw, and wherein the second end 83 of a        first screw cap is connected to the cover 73 of a second screw        cap at a fracture point 71.

However, now referring to FIG. 9, other embodiments of the presentinvention use modular screw caps, wherein the shank 85 and a cover 87having a central throughhole 89 are manufactured separately and thenassembled by overmolding, by fitting the shank through the throughholeof the cover. In these embodiments, the shanks can be provided as aplurality of shanks wherein the first end of a first shank is connectedto the second end of a second shank by a fracture point. FIG. 10 showsthe assembled modular embodiment.

In the embodiments of FIG. 11, the shank 90 (which primarily has anattachment function) is generally made of a strong and rigid firstmaterial that is slow to resorb. Preferably, the shank carries a highconcentration of the pharmaceutical. Also in the embodiment of FIG. 11,the cover 91 is made of a second material whose strength is usually notimportant (as it has no attachment function) and is usually relativelyquick to resorb. Preferably, the cover carries a high or relatively lowconcentration of the pharmaceutical.

In other embodiments of the present invention, the shank of the cap iscoated with a degradation resistant coating in order to retarddegradation of the shank and thereby prolong release of thepharmaceutical from within the shank. This is desirable because theshank has an attachment function and so its degradation may lead to anundesirable loosening of the drug-eluting component.

Now referring to FIG. 12, there is provided a spinal rod covercomprising an pharmaceutical compound, wherein the cover comprises:

-   -   a) a split-annulus defining a longitudinal axis.

In some embodiments of the present invention, the device covers a spinalrod implant 93, and is preferably in the form of a split-annulus 95, asplit-ring 97 or a coil 99. Preferably, the diameter of such a devicenearly coincides with that of the spinal rod implant, and is preferablyslightly smaller than that of the spinal rod implant, so as to provide asnap fit thereon. Flanges or tynes may also be provided on the device inorder to prevent device detachment. These features are manufactured fromslower degrading materials having a mechanical function. They may attachby wrap-around or interference attachment and be made of delayeddegradation biomaterials. Alternatively, the base device can be modifiedfor better cap attachment.

There are several benefits to using the rod cover device of the presentinvention. First, it possesses a relatively simple geometry. Second, asmost rods used in spinal surgery are simple cylinders, a single rodcover device of the present invention can accommodate the rods ofseveral different manufacturers. Third, the rod cover offers ease ofplacement because the rod always presents an orientation that lends toplacing a cover, unlike a screw cap that requires a unidirectionalapproach. In addition, because spinal rods extend virtually over theentire footprint of the conventional spinal implant system, it ispossible to cover a large percentage of the system's footprint by usingrod cover devices.

The dose of pharmaceutical delivered by the rod cover as well as itsduration can be increased by increasing the thickness, length, orsurface area of the rod cover.

Use of the rod cover device further allows the surgeon to concentratethe pharmaceutical along the length of the rod, rather than at specificpoints along the rod (such as the pedicle screw location). For example,if the surgeon desires to protect a small area, the surgeon can use asplit-ring embodiment of the rod cover device. If the surgeon desires toprotect a large area, the surgeon can use a split-annulus or coilembodiment of the rod cover device. In some embodiments, the rod coverdevice can be manufactured by an inexpensive extrusion manufacturingprocess, thereby lowering manufacturing costs.

Now referring to FIG. 13, there is provided a side view of a rod coverdevice 101 of the present invention attached to a spinal implant systemthat is implanted in a spine, wherein the system comprises rods 103 andscrews 105. This FIG. 13 can be contrasted with FIG. 4 in order toappreciate the difference in concentration profiles afforded by the capversus the rod cover. Whereas the screw cap provides a highconcentration [C] of the pharmaceutical present only in the regionsadjacent the screw, the rod cover provides high concentration virtuallyeverywhere along the length of the implant system. Moreover, it is notedthat the complex interior polyaxial surfaces of the pedicle screw arelocated very adjacent the ends of the rod cover devices. Therefore, itis believed that these complex interior polyaxial surfaces of thepedicle screw will likely be bathed in the pharmaceutical provided bythe ends of the rod cover devices. It appears that only the area aroundthe screw heads are far from the rod covers and so will have arelatively lower concentration of the pharmaceutical.

FIG. 14 a provides a typical cross-section of an assembled polyaxialpedicle screw 107 and rod 108 covered by a split annulus embodiment 109.It is observed that the screw has many complex interfaces that arewithin its interior and so are shielded from the patient's circulatoryand immune systems. Without wishing to be tied to a theory, it isbelieved that these shielded areas are the locations most susceptible todelayed and chronic infections. Bathing these surfaces in anti-microbialpharmaceutical may prevent these infections.

Now referring to FIGS. 14 b-c, preferably, the rod cover device of thepresent invention has a split annulus design. The split annulus 111preferably features a radius R1 that is just slightly smaller than theradius R2 of the corresponding rod 113, so that the rod covered can besnapped on and secured. Preferably, the rod cover describes an arc ofbetween about 200 degrees and about 300 degrees. If the angle is lessthan 200 degrees, the rod cover may not attach securely to the rod. Ifthe angle is greater than 300 degrees, there may be difficulty inproviding an opening large enough to allow the rod cover to envelope therod.

The material of construction for the rod cover typically is a homogenouscomposition, and is preferably amenable to extrusion processing. Whenthe rod cover is made by an extrusion process, the extruded piece mayadditionally be cut to length intra-operatively by the surgeon in orderto obtain the appropriately sized device. It is believed that theextruded rod cover would represent one of the least costly methods ofmaking the rod cover device of the present invention.

In some embodiments, the rod cover device is a segmented annulus havinga plurality of slits. Now referring to FIG. 15 a-b, there is provided aspinal rod cover 121 comprising a pharmaceutical compound, wherein thecover comprises:

a) an annular base 123 defining a longitudinal axis and comprising:

-   -   i) a plurality of slits 125 extending substantially        perpendicular to the longitudinal axis,    -   ii) a plurality of depressions 127 between the slits.        The plurality of slits allow the surgeon who has determined the        appropriate length of the rod cover to snap off the appropriate        length of the rod cover at one of the plurality of fracture        points beneath the slits. This provides the surgeon with an        ability to select an incremental rod cover length that        corresponds with the length of rod existing between adjacent        pedicle screws.

Of note, the segmented rod cover of FIGS. 15 a-b may also be made via anextrusion process. As shown in FIGS. 16 a-b, the material to be extruded131 enters the extruder 133 via its funnel 135, is sent forward by theextruder's ram 137 into a die 139 wherein it takes its extruded form.Prior to exiting the extruder, the extruded part is fed into a chopper141 that forms the plurality of slits at the desired spacing.

In some embodiments, the rod cover device comprises two components. Nowreferring to FIG. 17, there is provided a spinal rod cover 143comprising a pharmaceutical compound, wherein the cover comprises:

a) a split annulus 145 defining a longitudinal axis and comprising:

-   -   i) a plurality of slits 147 extending substantially        perpendicular to the longitudinal axis,    -   ii) a plurality of depressions 148 between the slits, and        b) a carrier material 149 associated with each depression,        wherein the carrier material carries the pharmaceutical        compound.

The split annulus has first and second faces each other and first andsecond ends. The snap-on annulus of the rod cover device is preferablyrigid and slow-resorbing. Its main function is to provide a means forattaching to the rod. The function of the carrier material is to deliverthe pharmaceutical to the tissue of interest.

Now referring to FIG. 18, there is provided a graph of the change inconcentration of a drug at a given location as a function of time for avariety of drug administration regimens. “MEC” refers to the “minimumeffective concentration” of a drug required to attain a giventherapeutic effect. “AMI” refers to the “Anti-Microbial Implant” of thepresent invention. “POA” refers to a prophylactic oral antibioticadministration. “OPTIMAL” refers to the optimal drug elution profile.

The optimal drug elution profile is linear and terminates abruptly withthe drug concentration always remaining above the MEC. In general,prophylactic oral antibiotics (POA) spike early and then dissipatewithin about a week of their administration. Typically, the implanteddevice volume and surface area are large compared to these variablesover time An implanted device that erodes or degrades over timetypically diminishes in both size and surface area over time—thus, ifelution depends on implant volume or surface area, drug dose isdependent on these time-based geometric changes. This is especially truefor surface-eroding delivery systems. Thus, the drug elution profile ofthe AMI of the present invention will likely experience a “mini-spike”and then diminish over time. The tail-end of the drug elution profile ofa surface-eroding AMI of the present invention will taper moreaggressively as its surface area is reduced.

Now referring to FIG. 19, there is provided a depiction of theconcentration profile over time of a drug eluting from a hydrolysabledrug delivery system. One such hydrolysable drug delivery system isPLLA. In such a system, it is expected that volume, drug diffusabilityfrom within the implant, surface area and erodability would beimportant. These systems typically have a more gradual elution profilewith few linear regions. Bulk material loss and surface changes arecombined with diffusion from the implanted PLLA delivery vehicle, sothree variables all impact the elution profile to make it non-linear andthus less predictable.

Now referring to FIG. 20, there is provided a concentration profile overtime of a drug eluting from a surface-eroding drug delivery system.Exemplary surface eroding hydrolysable drug delivery systems includepolysaccharides and linear anhydrides. In such a system, it is expectedthat volume, drug concentration and surface area would be important.These systems typically produce an initial concentration spike followedby a gradual diminishing ramp profile.

In some embodiments, the device is placed into bony voids created bysurgery in order to eliminate or reduce the formation of a post-surgicalhematoma—the bacterial petri dish that enables many post-operativeinfections.

Now referring to FIGS. 21 a-21 e, there are provided rod covers of thepresent invention having extensions. FIGS. 21 a-b show a single wideextension 211 extending from the annulus 210 for the length of the rodcover. FIG. 21 c shows a plurality of extensions 213 extending from theannulus. FIG. 21 c shows an extension 215 terminating in a head 217extending from the annulus.

Extensions of material from the rod cover are contemplated. Thesematerial extensions are contemplated to have mechanical or drug-elutingfunctions. Since the rod cover interfaces directly with the rod or thesides of the screw head in direct contact with the rod, a rod covermaterial extension could be placed proximal to a screw head (surroundingit or placed superficially) for either mechanical or drug-elutingpurposes. Placement of a drug eluting extension proximally to the screwhead would approximate complete coverage of the entire rod-screwconstruct with the locally eluted drug. Additionally, rod cover materialextensions could interface with local tissues either mechanically orpharmaceutically. A strut of material extending from the rod cover couldbe used to prevent soft tissue encroachment on a healing wound site.Similarly, a strut of material extending from the rod cover could beused to locate a drug-eluting depot distally from the rod and rod cover.Distal placement of the drug eluting depot would enable greater localpenetration/concentration of the eluted pharmaceutical agent. Finally,the material extension could be embodied as a sheet, flag, or tetherthat is attached at some point to the rod cover material. In this case,the material extension could be an entirely separate material systemwith a different function, such as a hemostat, an anti-adhesion barrier,a drug depot (pain medication or anti-bacterial compounds), etc. Thepurpose of attaching a separate device as an extension to the rod coveris to co-locate this new material or second device with the rod cover,thereby decreasing the propensity for migration of the materials awayfrom the rod.

Now referring to FIGS. 22 a-22 e, there are provided screw caps of thepresent invention having extensions. FIGS. 22 a-b show a plurality ofextension 221 extending laterally from the screw cap 222. FIG. 22 cshows an extension 223 axially extending from the screw cap 224. FIGS.22 d-e shows a fabric extension 225 attached to the screw cap 226.

Material extensions from the screw cap are also contemplated in thisinvention. The purpose of these extensions can be to provide cap-to-capscrew head connections, cap-to-rod connections, or combinations ofdevice interconnections. Additionally, the material extensions from thescrew cap can have mechanical functions with surrounding tissues. Forexample, a strut of screw cap material could be used to preventsurrounding soft tissues from touching one another or to prevent localsoft tissue encroachment on a wound space. Alternatively, the screw capextension could be used to deploy an eluting drug agent into thesurrounding tissues distal to the screw location. With a materialextension, screw cap drug-eluting materials are placed distally from thescrew cap and enable increased distribution and diffusion of the drugs.Additionally, a large bolus of material can be tethered to the screw capextension thereby placing a significant portion of drug eluting materialdistal to the screw cap location, but locally tethered to the screw cap.Finally, the screw cap material extension could be embodied as a sheetor flag of material, perhaps different from the screw cap material. Inone embodiment, such a material could be a woven textile of hemostatthat is attached to the screw cap. The purpose of such an embodimentwould be to positively co-locate a sheet of material with the screw cap,thereby decreasing this material's propensity to migrate in the woundafter implantation.

The rod cover and screw cap of the present invention may be made frombiocompatible materials that are either resorbable or non-resorbable.

In some embodiments, the rod cover and screw cap are non-resorbable.These non-resorbable devices also prevent bacterial colonization fromoccurring.

Preferred bioresorbable materials which can be used to make componentsof the present invention include bioresorbable polymers or copolymers,preferably selected from the group consisting of hydroxy acids,(particularly lactic acids and glycolic acids; caprolactone;hydroxybutyrate; dioxanone; orthoesters; orthocarbonates; andaminocarbonates. Preferred bioresorbable materials also include naturalmaterials such as chitosan, collagen, cellulose, fibrin, hyaluronicacid; fibronectin, and mixtures thereof. However, syntheticbioresorbable materials are preferred because they can be manufacturedunder process specifications which insure repeatable properties.

A variety of bioabsorbable polymers can be used to make the device ofthe present invention. Examples of suitable biocompatible, bioabsorbablepolymers include but are not limited to polymers selected from the groupconsisting of aliphatic polyesters, poly(amino acids),copoly(ether-esters), polyalkylenes oxalates, polyamides, tyrosinederived polycarbonates, poly(iminocarbonates), polyorthoesters,polyoxaesters, polyamidoesters, polyoxaesters containing amine groups,poly(anhydrides), polyphosphazenes, biomolecules (i.e., biopolymers suchas collagen, elastin, bioabsorbable starches, etc.) and blends thereof.For the purpose of this invention aliphatic polyesters include, but arenot limited to, homopolymers and copolymers of lactide (which includeslactic acid, D-,L- and meso lactide), glycolide (including glycolicacid), ε-caprolactone, p-dioxanone (1,4-dioxan-2-one), trimethylenecarbonate (1,3-dioxan-2-one), alkyl derivatives of trimethylenecarbonate, δ-valerolactone, β-butyrolactone, χ-butyrolactone,ε-decalactone, hydroxybutyrate, hydroxyvalerate, 1,4-dioxepan-2-one(including its dimer 1,5,8,12-tetraoxacyclotetradecane-7,14-dione),1,5-dioxepan-2-one, 6,6-dimethyl-1,4-dioxan-2-one, 2,5-diketomorpholine,pivalolactone, χ,χ-diethylpropiolactone, ethylene carbonate, ethyleneoxalate, 3-methyl-1,4-dioxane-2,5-dione,3,3-diethyl-1,4-dioxan-2,5-dione, 6,8-dioxabicycloctane-7-one andpolymer blends thereof. Poly(iminocarbonates), for the purpose of thisinvention, are understood to include those polymers as described byKemnitzer and Kohn, in the Handbook of Biodegradable Polymers, edited byDomb, et. al., Hardwood Academic Press, pp. 251-272 (1997).Copoly(ether-esters), for the purpose of this invention, are understoodto include those copolyester-ethers as described in the Journal ofBiomaterials Research, Vol. 22, pages 993-1009, 1988 by Cohn and Younes,and in Polymer Preprints (ACS Division of Polymer Chemistry), Vol.30(1), page 498, 1989 by Cohn (e.g. PEO/PLA). Polyalkylene oxalates, forthe purpose of this invention, include those described in U.S. Pat. Nos.4,208,511; 4,141,087; 4,130,639; 4,140,678; 4,105,034; and 4,205,399.Polyphosphazenes, co-, ter- and higher order mixed monomer-basedpolymers made from L-lactide, D,L-lactide, lactic acid, glycolide,glycolic acid, para-dioxanone, trimethylene carbonate and ε-caprolactonesuch as are described by Allcock in The Encyclopedia of Polymer Science,Vol. 13, pages 31-41, Wiley Intersciences, John Wiley & Sons, 1988 andby Vandorpe, et al in the Handbook of Biodegradable Polymers, edited byDomb, et al, Hardwood Academic Press, pp. 161-182 (1997). Polyanhydridesinclude those derived from diacids of the formHOOC—C₆H₄—O—(CH₂)_(m)—O—C₆H₄—COOH, where m is an integer in the range offrom 2 to 8, and copolymers thereof with aliphatic alpha-omega diacidsof up to 12 carbons. Polyoxaesters, polyoxaamides and polyoxaesterscontaining amines and/or amido groups are described in one or more ofthe following U.S. Pat. Nos. 5,464,929; 5,595,751; 5,597,579; 5,607,687;5,618,552; 5,620,698; 5,645,850; 5,648,088; 5,698,213; 5,700,583; and5,859,150. Polyorthoesters such as those described by Heller in Handbookof Biodegradable Polymers, edited by Domb, et al, Hardwood AcademicPress, pp. 99-118 (1997).

Preferably, the bioresorbable material is selected from the groupconsisting of poly(lactic acid) (“PLA”) and poly(glycolic acid) (“PGA”),and copolymers thereof. These materials are preferred because theypossess suitable strength and biocompatibility, display desirableresorption profiles, and have a long history of safe in vivo use. Ingeneral, PLA is a desirable because it typically has a resorption timeexceeding 12 months, whereas PGA resorbs fairly quickly (having aresorption time of less than 12 months). However, PLA can require manyyears to completely resorb, and so is more likely to produceforeign-body reactions. Therefore, more preferably, the material is aPLA/PGA copolymer, more preferably the copolymer comprises between 80 wt% and 99 wt % lactic acid (as PLA), and between 1 wt % and 20 wt %glycolic acid (as PGA). Copolymers within these ranges provide theproper balance between the strength and the resorption time of theligament.

The term “pharmaceutical” or “drug”, as used herein, refers to anysubstance used internally as a medicine for the treatment, cure, orprevention of a disease or disorder, and includes but is not limited toimmunosuppressants, antioxidants, anesthetics, analgesics,chemotherapeutic agents, steroids (including retinoids), hormones,antibiotics or anti-microbials, antivirals, antifungals,antiproliferatives, antihistamines, anticoagulants, antiphotoagingagents, melanotropic peptides, nonsteroidal and steroidalanti-inflammatory compounds, antipsychotics, and radiation absorbers,including UV-absorbers.

Non-limiting examples of pharmacological materials includeanti-infectives such as nitrofurazone, sodium propionate, antibiotics,including penicillin, tetracycline, oxytetracycline, chlorotetracycline,bacitracin, nystatin, streptomycin, neomycin, polymyxin, gramicidin,chloramphenicol, erythromycin, and azithromycin; sulfonamides, includingsulfacetamide, sulfamethizole, sulfamethazine, sulfadiazine,sulfamerazine, and sulfisoxazole, and anti-virals including idoxuridine;antiallergenics such as antazoline, methapyritene, chlorpheniramine,pyrilamine prophenpyridamine, hydrocortisone, cortisone, hydrocortisoneacetate, dexamethasone, dexamethasone 21-phosphate, fluocinolone,triamcinolone, medrysone, prednisolone, prednisolone 21-sodiumsuccinate, and prednisolone acetate; desensitizing agents such asragweed pollen antigens, hay fever pollen antigens, dust antigen andmilk antigen; vaccines such as smallpox, yellow fever, distemper, hogcholera, chicken pox, antivenom, scarlet fever, diphtheria toxoid,tetanus toxoid, pigeon pox, whooping cough, influenzae rabies, mumps,measles, poliomyelitic, and Newcastle disease; decongestants such asphenylephrine, naphazoline, and tetrahydrazoline; miotics andanticholinesterases such as pilocarpine, esperine salicylate, carbachol,diisopropyl fluorophosphate, phospholine iodide, and demecarium bromide;parasympatholytics such as atropine sulfate, cyclopentolate,homatropine, scopolamine, tropicamide, eucatropine, andhydroxyamphetamine; sympathomimetics such as epinephrine; sedatives andhypnotics such as pentobarbital sodium, phenobarbital, secobarbitalsodium, codeine, a-bromoisovaleryl) urea, carbromal; psychic energizerssuch as 3-(2-aminopropyl) indole acetate and 3-(2-aminobutyl) indoleacetate; tranquilizers such as reserpine, chlorpromayline, andthiopropazate; anesthetics, such as novicaine and bupivacaine;androgenic steroids such as methyl-testosterone and fluorymesterone;estrogens such as estrone, 17-flestradiol, ethinyl estradiol, anddiethyl stilbestrol; progestational agents such as progesterone,megestrol, melengestrol, chlormadinone, ethisterone, norethynodrel,19-norprogesterone, norethindrone, medroxyprogesterone and17-O-hydroxy-progesterone; humoral agents such as the Prostaglandins,for example PGEI, PGE2 and PGF2; antipyretics such as aspirin, sodiumsalicylate, and salicylamide; antispasmodics such as atropine,methantheline, papaverine, and methscopolamine bromide; antimalarialssuch as the 4-aminoquinolines, 8-aminoquinolines, chloroquine, andpyrimethamine, antihistamines such as diphenhydramine, dimenhydrinate,tripelennamine, perphenazine, and chlorphenazine; cardioactive agentssuch as dibenzhydroflume thiazide, flumethiazide, chlorothiazide, andaminotrate; nutritional agents such as vitamins, natural and syntheticbioactive peptides and proteins, including growth factors, cell adhesionfactors, cytokines, and biological response modifiers.

The active compound is included in the composition in an amountsufficient to deliver to the host patient an effective amount to achievea desired effect. The amount of drug or biologically active agentincorporated into the composition depends upon the desired releaseprofile, the concentration of drug required for a biological effect, andthe desired period of release of the drug.

The concentration of active compound in the composition will also dependon absorption, inactivation, and excretion rates of the drug as well asother factors known to those of skill in the art. It is to be noted thatdosage values will also vary with the severity of the condition to bealleviated. It is to be further understood that for any particularsubject, specific dosage regimens should be adjusted over time accordingto the individual need and the professional judgment of the personadministering or supervising the administration of the compositions, andthat the concentration ranges set forth herein are exemplary only andare not intended to limit the scope or practice of the claimedcomposition. The composition may be administered in one dosage, or maybe divided into a number of smaller doses to be administered at varyingintervals of time.

The biologically active substance is typically present in thecomposition in the range from about 0.1 percent to about 20 percent byweight, more particularly from about 0.5 percent to about 20 percent byweight relative to the total weight of the composition, and moretypically, between approximately 1 percent to about 15 percent byweight, and more. Another preferred range is from about 2 percent toabout 10 percent by weight. For very active agents, such as growthfactors, preferred ranges are less than 1% by weight, and less than0.0001%.

REFERENCES

-   1. J Bone Joint Surg (Br), 63:342-53, 1981-   2. J Bone Joint Surg (Br), 87(2): 249-56, 2005-   3. J. Neurosurg., 69: 687-91, 1988-   4. J. Neurosurg., 73:383-386, 1990-   5. JNeurosurg. 60:724-726, 1984.-   6. Spine 30(12):1460-5, 2005.-   7. Spine 28(13):1475-80, 2003.-   8. Spine 24(18):1909-12, 1999.-   9. Spine 26(18):1990-6, 2001.-   10. J Bone Joint Surg [Am] 77:524-9, 1995.-   11. J Neurosurg 69:687-91, 1988.-   12. N Engl J Med 350(14):1422-1429, 2004.-   13. 2003 communication from Johns Hopkins spine surgeon, Dr.    Sponseller.

1. A bone screw cap loaded with a pharmaceutical compound, wherein thecap fits substantially closely to a contour of a head of a bone screw.2. The bone screw cap of claim 1 comprising: a) a cover having aperimeter and a center.
 3. The bone screw cap of claim 2 furthercomprising: b) a shank extending downward from the cover.
 4. The cap ofclaim 3 wherein the cover and shank fit substantially closely to anouter contour of the head of the bone screw.
 5. The cap of claim 3wherein the cover and shank fit substantially closely to an innercontour of the head of the bone screw.
 6. The bone screw cap of claim 3further comprising: c) means for connecting the cap to the bone screw.7. The cap of claim 6 wherein the means comprises a flange.
 8. The capof claim 7 wherein the flange extends from the perimeter of the coverand engages a recess in the contour of the bone screw.
 9. The cap ofclaim 7 wherein the flange extends inward from the perimeter of thecover.
 10. The cap of claim 7 wherein the flange extends from the centerof the cover and engages a recess in the head of the bone screw.
 11. Thecap of claim 6 wherein the means comprises a recess.
 12. The cap ofclaim 11 wherein the recess extends into the perimeter of the cover andengages a flange in the contour of the bone screw.
 13. The cap of claim6 wherein the means comprises an adhesive or a curing composition. 14.The cap of claim 6 wherein the means comprises a snap-on connection. 15.The cap of claim 1 further comprising an extension.
 17. The cap of claim3 wherein the cover substantially defines a circle and the shanksubstantially defines an annulus.
 18. The cap of claim 3 wherein thecover and shank substantially define a hollow hemisphere.
 19. The cap ofclaim 3 wherein the shank extends downward from the perimeter of thecover.
 20. The cap of claim 3 wherein the shank extends downward fromthe center of the cover.
 21. The cap of claim 3 wherein the cover andshank are modular.
 23. The cap of claim 1 wherein the pharmaceuticalcompound is an anti-microbial compound.
 24. The cap of claim 1 whereinthe pharmaceutical compound is present as a coating.
 25. The cap ofclaim 1 wherein the pharmaceutical compound is embedded with the cap.26. A spinal rod cover comprising a pharmaceutical compound.
 27. Thecover of claim 26 further comprising a plurality of slits.
 28. The coverof claim 27 wherein further comprising a carrier material associatedwith each depression.
 29. The cover of claim 28 wherein the carriermaterial carries the pharmaceutical compound.
 30. The cover of claim 29wherein the pharmaceutical compound is an anti-microbial compound. 31.The cover of claim 26 wherein the annulus is a split annulus, ring orcoil.
 32. The cover of claim 26 further comprising an extension.
 33. Thecover of claim 26 further comprising a plurality of depressions betweenthe slits.
 34. A method of making a spinal rod assembly, comprising thesteps of: a) providing a spinal rod and a spinal rod cover comprising apharmaceutical compound, b) attaching the spinal rod cover to the spinalrod.
 35. A method of making a spinal screw assembly, comprising thesteps of: a) providing a spinal screw and a spinal screw cap comprisinga pharmaceutical compound, b) attaching the spinal screw cap to thespinal screw.
 36. A method of making a spinal screw assembly, comprisingthe steps of: a) providing a load bearing spinal component, b) providinga non-load bearing spinal component comprising a pharmaceuticalcompound, c) attaching the non-load bearing spinal component to the loadbearing spinal component.
 37. A spinal screw assembly, comprising thesteps of: a) a load bearing spinal component, b) a non-load bearingspinal component comprising a pharmaceutical compound, wherein thenon-load bearing spinal component is attached to the load bearing spinalcomponent.